Conclusive evidence of immune dysfunction after exposure of experimental animals to marijuana smoke or constituents has not been demonstrated. The first aim of this proposal is to establish maximum acute and chronic marijuana smoke exposure regimens in mice and rats which will allow assessment of potential immunosuppressive effects in the absence of general systemic toxicity. Established criteria of immunoselectivity will be used in setting these maxima. A modified Walton Automatic Smoking Machine will be used to expose animals to marijuana or placebo marijuana cigarette smoke or air. Delta9-THC will be used as a dosimetric marker for estimating the magnitude (Ct product) of smoke exposure. The Ct product of different exposure regimens will be compared to the levels of Delta9/-THC in plasma in animals receiving these exposures in order to quantify the relationship between the magnitude of smoke exposure and absorption of smoke constituents. The role of carbon monoxide poisoning in any immunotoxicities which may be found will be assessed. The second and third aims of this proposal are to determine whether dose-related increases in susceptibility to microbial infection and tumor growth, respectively, occur in subjects receiving different magnitudes of marijuana or placebo cigarette smoke. Resistance to systemic infectivity will be measured by the recovery of viable S. aureus organisms from tissue homogenates and blood of experimentally infected mice using the standard plate count method. In these studies, elevated numbers of viable bacteria recovered from smoke-treated animals as compared to sham-treated controls will be taken as evidence of immunosuppression. Resistance to localized infection will be measured by the severity of dermonecrosis (necrotic index) and the amount of early fluid exudate after subcutaneous injection of S. aureus. An elevated necrotic index or decreased fluid exudate in smoke-treated animals as compared to sham-treated ones will be considered evidence of immunosuppression. To measure the effects of marijuana smoke on cellular immunity, a mouse tumor heterograft assay in rats will be used. Increased palpable tumor volume and time-to-rejection in smoke-exposed as opposed to air-exposed rats will be considered as evidence of suppressed cellular immunity. The data generated in these studies should make it possible to assess whether occasional (acute) or habitual (chronic) marijuana use causes an increase in susceptibility to infection and tumor proliferation in animals.